Type I collagen is the most abundant protein in the human body. It is composed of two α1(I) polypeptides and one α2(I) polypeptides, which fold into a triple helix.1 Fibroproliferative disorders are characterized by excessive production of type I collagen by activated fibroblasts and myofibroblasts in tissues that normally do not synthesize type I collagen,2-5 and they are the major causes of mortality and morbidity, being associated with 45% of deaths in the United States.6 There is no cure for fibrosis, and excessive collagen production is usually irreversible.7 All complications of fibroproliferative disorders are due to excessive collagen production, and the molecular mechanism of excessive collagen synthesis must be elucidated to develop antifibrotic drugs. The biosynthesis of type I collagen has multiple steps; however, recently, it became evident that regulation of the stability of collagen mRNAs and their translation constitute the predominant mechanism for high-level synthesis in multiple cell types.8-12 
In the 5′ untranslated region of collagen α1(I), α2(I), and α1(III) mRNAs, there is a conserved 5′ stem-loop (5′SL) structure.13-15 We cloned LARP6, the protein that binds 5′SL with high affinity and specificity.16 This binding is necessary for high-level expression of type I collagen. We postulated that LARP6 binding serves to prevent premature translation of collagen mRNAs, allowing their subsequent coordinated translation on the membrane of the endoplasmic reticulum (ER).17 This coordination is evidenced by localization of collagen synthesis into discrete subcellular sites.16 Translation of collagen α1(I) and α2(I) mRNAs in close proximity to these sites may be needed to increase the local concentration of the polypeptides, which favors the formation of α1(I)/α2(I)/α1(I) heterotrimers. Heterotrimers of type I collagen are almost exclusively synthesized in all tissues,18 although the homotrimers of α1(I) polypeptides readily form if α2(I) polypeptide is not expressed.19,20 Folding of collagen triple helix starts with disulfide bonding of two a1(I) polypeptides and one α2(I) polypeptide at the C-terminal end, with subsequent folding into a triple helix. Disulfide-bonded collagen polypeptides were found to be associated with polysomes,21 suggesting that interchain bonding starts before the release of the polypeptides from the polysomes. Folding and post translational modifications of collagen polypeptides are in kinetic equilibrium, and slow folding results in hypermodification of the polypeptides. Hypermodified collagen peptides fold into an unstable triple helix, resulting in a phenotype of osteogenesis imperfecta.22,23 Therefore, translational elongation, the rate of modification, and the rate of folding are coordinated. TRAM2 protein, as part of translocons, associates the Ca2+ pump Serca2b with the translocons where collagen chains are elongated. It has been proposed that this increases local Ca2+ concentration to stimulate collagen-specific molecular chaperones, facilitating folding of the heterotrimer.12 Despite cloning and characterization of LARP6, the mechanism that coordinates the synthesis of type I collagen is poorly understood. In this work, we describe one key step in the synthesis of type I collagen by profibrotic cells—the interaction of collagen mRNAs with filaments composed of nonmuscle myosin.